1. Field of the Invention
The present invention is concerned with a process for the production of coarse-grained, anhydrous calcium monohydrogen phosphate (dicalcium phosphate anhydride), and a device for carrying out the process.
2. Description of Related Art
Two secondary dicalcium phosphates are known, namely, the anhydrous form CaHPO.sub.4 (DCPA), and the dihydrate CaHPO.sub.4.2H20 (DCPD). Both compounds occur in nature in crystalline form as monetite and brushite. Various processes for the production of the two compounds are known from the literature, the anhydride in particular being produced in aqueous solution at an elevated temperature by a precipitation reaction according to the following equation: EQU H.sub.3 PO.sub.4 +CaO.fwdarw.CaHPO.sub.4 +H20
The dihydrate typically is obtained at temperatures of less than 36.degree. C. and is slowly converted into the anhydride by heating to temperatures above 36.degree. C.
These products have found a certain measure of interest in dental chemistry because of their use with a fine-grained structure as cleaning materials in toothpastes. The anhydride is the product with the greater hardness, and it is therefore used for the adjustment of the abrasive properties, and for smokers' pastes.
In the pharmaceutical industry, coarse-grained dicalcium phosphate dihydrate is used to a large extent as a carrier substance in direct tabletting. For the achievement of a reproducible tablet having a definite breaking strength at the same pressing force, the following requirements are required for the tabletting adjuvant: for uniform dosing in the tabletting press, the product must a) be readily pourable, which means the product must have a coarse grain structure in the range of 45 to 300 .mu.m and a narrow grain distribution within this range, and b) the crystal form should be almost spherical. DCPD fulfills these requirements very well. However, the field of use of DCPD is limited to active material combinations which are not sensitive to water since the dihydrate slowly releases water above 40.degree. C., and thereby changes incongruently.
Therefore, the use of dicalcium phosphate anhydride is of increasing interest for the direct tabletting of pharmaceutical products which is not limited to active material combinations which are not sensitive to water. However, in the case of the direct precipitation of DCPA, a very fine grained material is preponderantly obtained which cannot be tabletted directly. Therefore, there has long been a need for the production of a coarse-grained dicalcium phosphate anhydride for use in direct tabletting.
Numerous processes are known for the production not only of DCPD but also of DCPA: Gmelin, Vol. 28, Part B, II, page 1167; EP 0 210 661 from DCPD granulate by the removal of water; U.S. Pat. No. 3,488,145 by crystallizing out DCPA at 80.degree. C., formation from phosphorus pentoxide and calcium oxide at 40.degree. C. with a grain size greater than 10 .mu.m; GB 1,304,218, production of DCPD and conversion into DCPA by heating the suspension; DE C. 21 53 725, precipitation from excess phosphoric acid with calcium oxide/calcium carbonate.
However, a disadvantage of all precipitation reactions which yield DCPA according to the processes described in the literature is that the DCPA is obtained in very finely-divided form and thus is not directly suitable for tabletting (see the remarks made in EP 0 210 661, page 2, line 11). As is known in the art, products produced by such processes have an average grain diameter of less than 50 .mu.m when underground.
According to the known processes for the production of dicalcium phosphate anhydride, milk of lime is, for example, introduced into dilute phosphoric acid, the phosphoric acid solution thereby being heated to at least 70.degree. C. Subsequently, with vigorous stirring, highly concentrated milk of lime is added thereto as quickly as possible until a pH value of 6.5 is achieved in the resultant suspension, whereafter the reaction is practically finished. In the filtrate obtained after the separation of the solid material, there are generally found about 5 mg/1 of phosphorus pentoxide. The introduction of the milk of lime usually takes place by allowing the suspension to run in from the lid of the reaction vessel.
In the case of such a procedure, there is obtained a finely-divided material which, because of its fineness, can, in part, only be filtered with difficulty. A precipitation at comparatively low temperatures, as well as a slow introduction of the milk of lime, results in a co-precipitation of the dihydrate.
If an attempt is made to increase the average grain diameter by measures such as seeding of the reaction batch, longer residence times during the crystallization, lower precipitation temperatures or higher dilution of the reaction solutions, then only a small effect is obtained in the grain size.
The "coarser" crystals forming in purely statistical distribution can be separated by purely mechanical processes from the product stream by screening and/or sieving but the yield in the case of this procedure is extremely small. For this reason, it has been suggested to produce tablettable DCPA products by the roundabout way of drying DCPD (see EP 0 210 661). In addition to the precipitation, this process requires a compacting step of the DCPD and an energy-intensive drying to yield DCPA. This drying step is rather problematical since the separation of water from DCPD at temperatures of from 40.degree. to 150.degree. C. proceeds very slowly but, on the other hand, the product must not be overheated since, at higher temperatures, a further reaction to dicalcium diphosphate very easily takes place.
Therefore, there exists a need to provide a simple and economic process for the production of coarse crystalline dicalcium phosphate anhydride which, by compression, has a grain size sufficient for direct tabletting.